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Thomas Kozlowski, OD Trans-Synaptic Degeneration in Multiple Sclerosis and the Evolving Role of OCT I. Case History Patient Demographics o 33yo WF Chief Complaint o Routine follow-up to monitor visual field loss secondary to Multiple Sclerosis Ocular History o Visual Field Defect secondary to Multiple Sclerosis No history of optic neuritis o Dry Eye Syndrome o Hyperopia o (-)eye injuries or surgeries Ocular Medications o Artificial Tears Medical History o Multiple Sclerosis (Relapsing-Remitting) Diagnosed 01/30/13 Brain MRI (01/30/13) Lumbar Puncture (02/01/13) h/o copaxone treatment, currently untreated (patient is hesitant and unwilling to take medication) o Asthma, Obesity, PTSD, Depression, Anxiety Medications o Albuterol, flunisolide, citalopram, lorazepam, levothyroxine, multivitamin II. Pertinent Findings (01/27/15) Visual acuity: 20/20 OD,OS (sc) Color Vision: Normal EOMs: S+F, (-)pain or diplopia Pupils: ERRL, (-)APD Additional Testing o HVF 30-2 01/30/13: Incomplete, incongruous (OS>OD) right hemianopia 02/27/13: same as above, mild improvement 09/26/13: same as above, mild improvement 01/27/15: same as above, OD essentially resolved, OS mildly improved o Spectralis OCT: RNFL 01/30/13: Global 99/103, no flags 02/27/13: Global 96/103, no flags 03/04/14: Global 83/87 OD Flags: Temporal, BDL Global OS Flags: ST, IT, BDL Temporal Significant progression! 01/27/15: Global 81/86 (same flags as previous) Overall stable o Spectralis OCT: Posterior Pole Analysis Interpretation Total Thickness: 276 OD, 263 OS OD: thinning of inner retinal layers nasal to fovea respecting the vertical midline OS: thinning of inner retinal layers temporal to fovea respecting the vertical midline Impression: pattern of retinal thinning correlates with pattern and severity of visual field III. Differential Diagnosis Addressed in Discussion IV. Diagnosis and Discussion Multiple Sclerosis o Epidemiology o Pathogenesis, disease course o Diagnosis Role of MRI o Symptoms o Visual Sequelae Blurred vision, visual field defects, color vision desaturation Optic neuritis Role of OCT in the Management of MS Patients o Retinal changes in MS Layer-specific atrophy RNFL, GCL, INL? Role of Peripapillary RNFL, Macular Volume scans o A. Retinal Damage in MS with Optic Neuritis (MSON) Optic neuritis as presenting symptom in 15-20% of MS patients, affects 50-70% throughout course of disease Pathogenesis Optic atrophy, pallor of optic nerve OCT Findings Loss of approximately 20 microns after ON 20% loss in RNFL thickness o B. Retinal Damage in MS with No Optic Neuritis (MSNON) Surprisingly, RNFL reduction has also been observed in eyes with MS and no history of optic neuritis Mean reduction = 7-10 microns thinner than normal controls Mean RNFL decrease/year (microns) in MS patients vs. normal Differential Diagnosis 1. Subclinical inflammation of optic nerve? 2. Primary retinal pathology? 3. Retrograde trans-synaptic degeneration of retinal axons Visual pathway review Pathogenesis: optic radiation damage causing retinal thinning Evidence in CVA patients MRI, OCT evidence HVF/OCT correlation in this patient as evidence of trans-synaptic degeneration of nerve axons secondary to MS o Role of OCT in Managing MS Patients: Present and Future Relationship between OCT and brain atrophy Evidence exists to support the idea that retinal degeneration measured by OCT reflects degree of neurologic degeneration, suggesting OCT measurements may be useful in measuring CNS damage and disease progression If RNFL thinning is indeed correlated with global brain atrophy and disease progression, OCT may become an essential tool in the care of these patients Noninvasive, inexpensive, objective, sensitive May lower threshold for initiation of treatment V. Conclusions Evidence exists to support the theory of trans-synaptic degeneration of retinal axons occurring in MS. This degeneration can be measured by OCT, and may be a marker of overall disease progression. Currently, the role of OCT in managing MS patients is not clearly defined. It is now complementary to MRI and general neurologic examination. As technology evolves and more clinical studies are completed, it is likely the role of OCT will become more and more relevant in monitoring progression in patients with MS, possibly even becoming standard of care. o Evolving role of the OD in the management of MS patients Bibliography Balcer L et al. “Vision and vision-related outcome measures in multiple sclerosis,” Brain 2015; 138: 11-27. Beatty RM et al. “Direct demonstration of trans-synaptic degeneration in the human visual system: a comparison of retrograde and anterograde changes," Journal of Neurology, Neurosurgery, and Psychiatry 1982; 45: 143-46. Belk L et al. “Current and future potential of retinal optical coherence tomography in multiple sclerosis with and without optic neuritis,” Neurodegenerative Disease Management 2014; 4(2), 165-76. Calabresi P et al. “Retinal pathology in multiple sclerosis: insights into the mechanism of neuronal pathology,” Brain 2010: 133; 1575-77 Gabilondo I et al. “Trans-Synaptic Neuronal Degeneration in the Visual Pathway in Multiple Sclerosis,” Ann Neurol 2014; 75: 98-107. Gonzalez-Lopez J et al. “Comparative Diagnostic Accuracy of Ganglion Cell-Inner Plexiform and Retinal Nerve Fiber Layer Thickness Measures by Cirrus and Spectralis Optical Coherence Tomography in Relapsing-Remitting Multiple Sclerosis,” Biomed Research International Volume 2014, Article 128517. Guedes M et al. “Acquired retrograde transynaptic degeneration,” BMJ Case Reports 2011; doi:10.1136/bcr.08.2011.4653. Keller J et al. “Lesions in the Posterior Visual Pathway Promote Trans-Synaptic Degeneration of Retinal Ganglion Cells,” Plos One May 2014, Volume 9, Issue 5. Martinez-Lapiscina E et al. “The multiple sclerosis visual pathway cohort: understanding neurodegeneration,” BMC Research Notes 2014, 7:910. Sinnecker T et al. “Optic radiation damage in multiple sclerosis is associated with visual dysfunction and retinal thinning – an ultrahigh-field MR pilot study,” Eur Radiol (2015) 25:122–131. Sriram P. “Transsynaptic Retinal Degeneration in Optic Neuropathies: Optical Coherence Tomography Study,” Investigative Ophthalmology & Visual Science, March 2012, Vol. 53, No. 3. Zimmerman H et al. “Optical coherence tomography for retinal imaging in multiple sclerosis,” Degenerative Neurological and Neuromuscular Disease 2014:4 153–162